A collaborative linkage study of breast cancer families that are not segregating mutations at either the BRCA1 or BRCA2 loci is ongoing. Collaborators in Finland, Sweden and Iceland are working together with NHGRI to add more families to the data set. Genotyping of several candidate regions and a genome wide scan have been performed on these samples. Linkage analysis is ongoing and a paper was published in PNAS in early 2000 suggesting the possibility of an additional locus (BRCA3) about 20 cM from the BRCA2 locus. Fine mapping of positive regions is also ongoing. We have performed additional mutation detection, genotyping and analysis to show that the positive linkage evidence at 13q21-22 is not likely to be due to contamination of our sample by undetected BRCA2 families. These results were presented at a recent UICC cancer meeting in Beijing, China and at the 2001 meeting of the American Society of Human Genetics. A paper detailing these results was completed and submitted in this fiscal year. Families that did not appear linked to BRCA1, BRCA2 or this novel BRCA3 locus have been genotyped for a genome scan panel of marker loci. Several regions showed some evidence for linkage and the regions with the strongest evidence for linkage are currently being followed up with fine mapping studies. A paper on the fine-structure of this genetic region was published in this fiscal year. Results of the fine mapping analyses were presented at the recent International Genetic Epidemiology Society meeting and at the 2001 meeting of the American Society of Human Genetics. A paper detailing these results has also been completed and submitted in this fiscal year. This project is ongoing. Additional genotyping is being performed at present and these data will be analyzed in the next fiscal year.